In-flow photooxygenation of aminothienopyridinones generates PTP4A3 phosphatase inhibitors

Abstract

The disclosure provides compounds that inhibit protein tyrosine phosphatase, such as protein tyrosine phosphatase 4A3 (PTP4A3). The disclosure also provides pharmaceutical compositions, uses, and methods of using the compounds, such as in the treatment of cancers. (I), wherein X is O or NH.

We claim: 
     
       1. A compound according to Formula (I), or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein
 X is O or NH; and 
 (linker) is a linker moiety. 
 
     
     
       2. The compound or pharmaceutically acceptable salt thereof according to  claim 1 , wherein —X-(linker)- is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
       3. The compound or pharmaceutically acceptable salt thereof according to  claim 1 , wherein the compound is of the formula (EJR-876-34): 
       
         
           
           
               
               
           
         
       
     
     
       4. The compound or pharmaceutically acceptable salt thereof according to  claim 1 , wherein the compound is of the formula (EJR-876-35): 
       
         
           
           
               
               
           
         
       
     
     
       5. The compound or pharmaceutically acceptable salt thereof according to  claim 1 , wherein the compound is of the formula (EJR-887-24): 
       
         
           
           
               
               
           
         
       
     
     
       6. The compound or pharmaceutically acceptable salt thereof according to  claim 1 , wherein the compound is of the formula (EJR-887-35): 
       
         
           
           
               
               
           
         
       
     
     
       7. A method for treating a subject suffering from cancer, the method comprising administering to the subject a therapeutically effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof to treat the cancer. 
     
     
       8. The method according to  claim 7 , wherein the cancer is selected from the group consisting of colorectal cancer, breast cancer, ovarian cancer, cervical cancer, lung cancer, liver cancer, stomach cancer, stromal cancer, leukemia, and lymphoma. 
     
     
       9. The method according to  claim 8 , wherein the cancer is breast cancer or ovarian cancer. 
     
     
       10. The method according to  claim 9 , wherein the cancer is triple negative breast cancer or advanced ovarian cancer. 
     
     
       11. A method for inhibiting a protein-tyrosine phosphatase in a cell, comprising contacting the cell with a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
       12. The method according to  claim 11 , wherein the protein tyrosine phosphatase is protein tyrosine phosphatase 4A3 (PTP4A3). 
     
     
       13. A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof, according to  claim 1  in admixture with a pharmaceutically acceptable carrier.